Special Issue "Chronic Lymphocytic Leukemia: Therapy and Outcome"

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: 1 October 2022 | Viewed by 5987

Special Issue Editor

Dr. Andrea Visentin
E-Mail Website
Guest Editor
Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, Italy
Interests: chronic lymphocytic leukemia; hairy cell leukemia; Hodgkin lymphoma; B cell receptor; targeted therapy; BCL2 inhibitor; BTK inhibitor; prognostic factor
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Special Issue Information

Dear Colleagues,

In the last 15 years, our understanding of chronic lymphocytic leukemia has been revolutionized thanks to significant insights into the molecular biology of the disease and the interplay between neoplastic cells and the surrounding microenvironment. The identification of molecules which are pivotal to the survival of malignant cells has allowed us to develop targeted therapies (monoclonal antibodies, kinase inhibitors and BH3-mimetics) that have become the cornerstone of chronic lymphocytic leukemia treatment. Despite these advances, the disease remains incurable and hypogammaglobulinemia, infections, and second primary malignancies still impinge upon patients’ quality of life.

For this Special Issue, we are pleased to invite you to submit original research articles and reviews on any aspect of chronic lymphocytic leukemia are welcome. Research areas may include (but are not limited to) diagnostic pitfall, prognostic factor, predictive factors, critical signaling pathways, comorbidities, targeted therapies, management of kinase inhibitors, Richter syndrome, supporting therapies, and quality of life.

We look forward to receiving your contributions.

Dr. Andrea Visentin
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic lymphocytic leukemia
  • microenvironment
  • BTK inhibitors
  • BCL2 inhibitors
  • PI3K inhibitors
  • infection
  • prognostic factors
  • predictive factors
  • Richter syndrome

Published Papers (6 papers)

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Research

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Article
Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis
Curr. Oncol. 2022, 29(6), 4245-4259; https://doi.org/10.3390/curroncol29060339 - 14 Jun 2022
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Abstract
Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and [...] Read more.
Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and safety of lenalidomide maintenance are still debated. Randomized controlled trials published before March 2022 were retrieved from databases. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Trial sequential analysis examined analytical power in primary outcomes. Secondary outcomes were Grade 3–4 neutropenia, treatment discontinuation (TD), serious adverse events (SAE), and fatal adverse events (FAE). Hazard (HR) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Four articles (733 patients) met the selection criteria. Lenalidomide maintenance was associated with a statistically significant effect in prolonging PFS (HR, 0.43; 95% CI, 0.28–0.68; I2 = 57%) and higher proportion of SAE (OR 4.64; 95% CI 2.96–7.26; I2 = 0%) and exhibited no difference in OS (HR, 0.62; 95% CI, 0.29–1.30; I2 = 52%) observation/placebo. It showed no significant difference compared with observation/placebo regarding Grade 3–4 neutropenia (OR 2.30; 95% CI 0.84–6.28; I2 = 81%), TD (OR 0.76; 95% CI 0.29–1.99; I2 = 84%), and FAE (OR 0.86; 95% CI 0.28–2.63; I2 = 0%). Lenalidomide maintenance can prolong PFS in CLL. Further studies should verify its effect on OS. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)
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Article
Invasive Fungal Disease in Patients with Chronic Lymphocytic Leukemia in Japan: A Retrospective Database Study
Curr. Oncol. 2022, 29(5), 3242-3251; https://doi.org/10.3390/curroncol29050264 - 04 May 2022
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Abstract
Invasive fungal disease (IFD) is an important cause of morbidity and mortality in patients with hematological malignancies. As chronic lymphocytic leukemia (CLL) is a rare hematological malignancy in Japan, IFD incidence in Japanese patients with CLL is unclear. This study aimed to investigate [...] Read more.
Invasive fungal disease (IFD) is an important cause of morbidity and mortality in patients with hematological malignancies. As chronic lymphocytic leukemia (CLL) is a rare hematological malignancy in Japan, IFD incidence in Japanese patients with CLL is unclear. This study aimed to investigate IFD incidence in Japanese patients with CLL. This retrospective cohort study used data of patients with CLL registered between April 2008 and December 2019 in the Medical Data Vision database (n = 3484). IFD incidence after CLL diagnosis in the watch-and-wait (WW) and drug therapy (DT) groups was 1.5% and 9.2%, respectively. The most common type of IFD was invasive aspergillosis (28.1%). Cox proportional hazards multivariate analysis revealed that DT (hazard ratio [HR]: 2.13) and steroid use (HR: 4.19) were significantly associated with IFD occurrence. IFD incidence was significantly higher in the DT group than in the WW group (log-rank p < 0.001); however, there was no significant between-group difference in the time to IFD onset or the type of IFD (p = 0.09). This study determined the incidence of IFD in patients with CLL during WW. Physicians should monitor for IFD, even among patients with CLL undergoing the WW protocol. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)
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Article
Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors
Curr. Oncol. 2021, 28(4), 2439-2451; https://doi.org/10.3390/curroncol28040223 - 01 Jul 2021
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Abstract
In B-chronic lymphocytic leukemia (B-CLL), the interaction between leukemic cells and the microenvironment promotes tumor cell survival. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to [...] Read more.
In B-chronic lymphocytic leukemia (B-CLL), the interaction between leukemic cells and the microenvironment promotes tumor cell survival. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to ibrutinib call for new therapeutic strategies. The purpose of the current study was to investigate the ability of ibrutinib plus the MDM2-inhibitor nutlin-3 to counteract the tumor microenvironment protective effect. We observed that primary B-CLL cells cultivated in microenvironment mimicking conditions were protected from apoptosis by the up-regulation of c-MYC and of p53. In the same setting, combined treatments with ibrutinib plus nutlin-3 led to significantly higher levels of apoptosis compared to the single treatments, counteracting the c-MYC up-regulation. Moreover, the combination induced high p53 levels and a significant dissipation of the mitochondrial membrane potential, together with BAX cleavage in the more active p18 form and phospho-BAD down-regulation, that are key components of the mitochondrial apoptotic pathway, enhancing the apoptosis level. Our findings propose a new therapeutic strategy to overcome the tumor microenvironment protection involved in B-CLL resistance to drugs, with possible clinical implications also for other hematologic and solid tumors for which ibrutinib is considered a therapeutic option. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)
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Review

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Review
CAR T Cell Therapy for Chronic Lymphocytic Leukemia: Successes and Shortcomings
Curr. Oncol. 2022, 29(5), 3647-3657; https://doi.org/10.3390/curroncol29050293 - 18 May 2022
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Abstract
Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other [...] Read more.
Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)
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Other

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Case Report
Two Distinct Clinical Patterns of Ibrutinib-to-Venetoclax Transition in Relapsed Chronic Lymphocytic Leukemia Patients
Curr. Oncol. 2022, 29(4), 2792-2797; https://doi.org/10.3390/curroncol29040227 - 15 Apr 2022
Cited by 1 | Viewed by 805
Abstract
Patients with chronic lymphocytic leukemia (CLL) relapsing on ibrutinib are often treated with the Bcl-2 inhibitor venetoclax. However, the transition from one agent to another poses some clinical challenges due to disease flares sometimes occurring right after ibrutinib interruption. Here, we describe three [...] Read more.
Patients with chronic lymphocytic leukemia (CLL) relapsing on ibrutinib are often treated with the Bcl-2 inhibitor venetoclax. However, the transition from one agent to another poses some clinical challenges due to disease flares sometimes occurring right after ibrutinib interruption. Here, we describe three clinical vignettes highlighting two distinct patterns of ibrutinib-to-venetoclax transition. While patients following the favorable pattern transited to venetoclax without experiencing disease flare, the one patient who took the unfavorable path showed rapid disease rebound, with large-cell transformation occurring one week after ibrutinib interruption. A high burden of BTK and PLCG2 mutations was found only in patients with the favorable transition pattern, suggesting that removing BTK inhibition might be particularly harmful if CLL cells are progressing through mechanisms external to the BTK axis. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)
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Case Report
Primary Myelofibrosis Occurring during Targeted Therapy for Chronic Lymphocytic Leukemia: A Report of Two Cases
Curr. Oncol. 2022, 29(3), 1455-1460; https://doi.org/10.3390/curroncol29030122 - 27 Feb 2022
Viewed by 838
Abstract
The disease course of chronic lymphocytic leukemia (CLL) is frequently characterized by the occurrence of various complications, such as second primary cancer, which can impact patients’ prognoses. While therapies for CLL have evolved tremendously in the past decades, overlooking the possibility of rare [...] Read more.
The disease course of chronic lymphocytic leukemia (CLL) is frequently characterized by the occurrence of various complications, such as second primary cancer, which can impact patients’ prognoses. While therapies for CLL have evolved tremendously in the past decades, overlooking the possibility of rare neoplasms that arise along with CLL may hinder the benefit that these therapies grant to patients. Moreover, the ability of newer therapies to alter the landscape of these complications is still largely unknown. Primary myelofibrosis (PMF) is not commonly associated with CLL, with only a few cases reported in the literature, with little information regarding the clinico-biological features and the optimal management for these associated conditions. Here, we report two unusual cases of PMF that occurred a few months after the start of therapy for CLL with targeted agents (ibrutinib and venetoclax). Both cases represented a diagnostic and therapeutic challenge, underscoring the need for clinicians to remain vigilant about the possible co-occurrence of these two hematological malignancies, especially in the era of targeted therapy for CLL. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)
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